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Find video protocols related to scientific articles indexed in Pubmed.
Predicting When to Administer Blood Products During Tactical Aeromedical Evacuation: Evaluation of a US Model.
J Spec Oper Med
PUBLISHED: 12-01-2014
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The administration of blood products to battlefield casualties in the prehospital arena has contributed significantly to the survival of critically injured patients in Afghanistan over the past 5 years. Given as part of an established military "chain of survival," blood product administration has represented a step-change improvement in capability for both UK and US tactical aeromedical evacuation (TACEVAC) platforms. The authors explore current concepts, analyzing and exploring themes associated with early use of blood products (fresh frozen plasma [FFP] and red blood cells [RBCs]), and they compare and evaluate a US/UK study analyzing the differences and recommending future strategy. The subject matter expert (SME) consensus guidelines developed for use by the US Army Air Ambulance units commonly known as call sign "DUSTOFF." These TACEVAC assets in Afghanistan were validated in this retrospective study. Using statistical analysis, the authors were able to ascertain that the current DUSTOFF SME?derived guidelines offer a sensitivity of 63.04% and a specificity of 89.07%. By adjusting the indicators to include a single above-ankle amputation with a systolic blood pressure (SBP) less than 90mmHg and pulse greater than 120/min, the sensitivity could be increased to 67.39% while maintaining the specificity at 89.07%. In our data set, a single amputation above the ankle, in combination with an SBP of less than 100mmHg and a pulse of greater than 120/min, increased the sensitivity to 76% but with a slight drop in specificity to 86%. Further study of military prehospital casualty data is under way to identify additional physiological parameters that will allow simple scoring tools in the remote setting to guide the administration of prehospital blood products.
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Can Urinary PCA3 Supplement PSA in the Early Detection of Prostate Cancer?
J. Clin. Oncol.
PUBLISHED: 11-12-2014
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Given the limited sensitivity and specificity of prostate-specific antigen (PSA), its widespread use as a screening tool has raised concerns for the overdiagnosis of low-risk and the underdiagnosis of high-grade prostate cancer. To improve early-detection biopsy decisions, the National Cancer Institute conducted a prospective validation trial to assess the diagnostic performance of the prostate cancer antigen 3 (PCA3) urinary assay for the detection of prostate cancer among men screened with PSA.
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Diminished testing benefits in young adults with attention-deficit hyperactivity disorder.
Memory
PUBLISHED: 11-12-2014
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Memory retrieval has been shown to enhance the long-term retention of tested material; however, recent research suggests that limiting attention during retrieval can decrease the benefits of testing memory. The present study examined whether testing benefits are reduced in young adults with attention-deficit hyperactivity disorder (ADHD). College students with and without ADHD read three short prose passages, each followed by a free recall test, a restudy period or a distractor task. Two days later participants recalled the passages. Although participants without ADHD did not show a significant benefit of testing over restudying, testing did produce recall benefits relative to not taking a test. These testing benefits were diminished in participants with ADHD, who did not show any advantage of testing over either restudying or no test. The absence of testing benefits in the ADHD group is likely due in part to decreased recall on the initial test. These findings have implications for improving educational practices among individuals with ADHD and also speak to the need to examine individual differences in the effectiveness of testing as a learning strategy.
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Identifying actionable targets through integrative analyses of GEM model and human prostate cancer genomic profiling.
Mol. Cancer Ther.
PUBLISHED: 11-09-2014
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Copy number alterations (CNAs) are among the most common molecular events in human prostate cancer genomes and are associated with worse prognosis. Identification of the oncogenic drivers within these CNAs is challenging due to the broad nature of these genomic gains or losses which can include large numbers of genes within a given region. Here we profiled the genomes of four genetically engineered mouse prostate cancer models that reflect oncogenic events common in human prostate tumors, with the goal of integrating these data with human prostate cancer datasets to identify shared molecular events. Met was amplified in 67% of prostate tumors from Pten p53 prostate conditional null mice and in approximately 30% of metastatic human prostate cancer specimens, often in association with loss of PTEN and TP53. In murine tumors with Met amplification, Met copy number gain and expression was present in some cells but not others, revealing intratumoral heterogeneity. Forced MET overexpression in non-MET amplified prostate tumor cells activated PI3K and MAPK signaling and promoted cell proliferation and tumor growth, whereas MET kinase inhibition selectively impaired the growth of tumors with Met amplification. However, the impact of MET inhibitor therapy was compromised by the persistent growth of non-Met amplified cells within Met-amplified tumors. These findings establish the importance of MET in prostate cancer progression but reveal potential limitations in the clinical use of MET inhibitors in late state prostate cancer.
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Borrelia burgdorferi Arthritis-Associated Locus Bbaa1 Regulates Lyme Arthritis and K/B×N Serum Transfer Arthritis through Intrinsic Control of Type I IFN Production.
J. Immunol.
PUBLISHED: 11-08-2014
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Localized upregulation of type I IFN was previously implicated in development of Borrelia burgdorferi-induced arthritis in C3H mice, and was remarkable due to its absence in the mildly arthritic C57BL/6 (B6) mice. Independently, forward genetics analysis identified a quantitative trait locus on Chr4, termed B. burgdorferi-associated locus 1 (Bbaa1), that regulates Lyme arthritis severity and includes the 15 type I IFN genes. Involvement of Bbaa1 in arthritis development was confirmed in B6 mice congenic for the C3H allele of Bbaa1 (B6.C3-Bbaa1), which developed more severe Lyme arthritis and K/B×N model of rheumatoid arthritis (RA) than did parental B6 mice. Administration of a type I IFN receptor blocking mAb reduced the severity of both Lyme arthritis and RA in B6.C3-Bbaa1 mice, formally linking genetic elements within Bbaa1 to pathological production of type I IFN. Bone marrow-derived macrophages from Bbaa1 congenic mice implicated this locus as a regulator of type I IFN induction and downstream target gene expression. Bbaa1-mediated regulation of IFN-inducible genes was upstream of IFN receptor-dependent amplification; however, the overall magnitude of the response was dependent on autocrine/paracrine responses to IFN-?. In addition, the Bbaa1 locus modulated the functional phenotype ascribed to bone marrow-derived macrophages: the B6 allele promoted expression of M2 markers, whereas the C3H allele promoted induction of M1 responses. This report identifies a genetic locus physically and functionally linked to type I IFN that contributes to the pathogenesis of both Lyme and RA.
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The impact of cooking classes on food-related preferences, attitudes, and behaviors of school-aged children: a systematic review of the evidence, 2003-2014.
Prev Chronic Dis
PUBLISHED: 11-07-2014
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Cooking programs have been used to promote healthful eating among people of all ages. This review assesses the evidence on childhood cooking programs and their association with changes in food-related preferences, attitudes, and behaviors of school-aged children.
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Strength-Training Protocols to Improve Deficits in Participants With Chronic Ankle Instability: A Randomized Controlled Trial.
J Athl Train
PUBLISHED: 11-04-2014
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Context :? Although lateral ankle sprains are common in athletes and can lead to chronic ankle instability (CAI), strength-training rehabilitation protocols may improve the deficits often associated with CAI. Objective :? To determine whether strength-training protocols affect strength, dynamic balance, functional performance, and perceived instability in individuals with CAI. Design : ?Randomized controlled trial. Setting :? Athletic training research laboratory. Patients or Other Participants :? A total of 39 individuals with CAI (17 men [44%], 22 women [56%]) participated in this study. Chronic ankle instability was determined by the Identification of Functional Ankle Instability method, and participants were randomly assigned to a resistance-band-protocol group (n = 13 [33%] age = 19.7 ± 2.2 years, height = 172.9 ± 12.8 cm, weight = 69.1 ± 13.5 kg), a proprioceptive neuromuscular facilitation strength-protocol group (n = 13 [33%], age = 18.9 ± 1.3 years, height = 172.5 ± 5.9 cm, weight = 72.7 ± 14.6 kg), or a control group (n = 13 [33%], age = 20.5 ± 2.1 years, height = 175.2 ± 8.1 cm, weight = 70.2 ± 11.1 kg). Intervention(s) : ?Both rehabilitation groups completed their protocols 3 times/wk for 6 weeks. The control group did not attend rehabilitation sessions. Main Outcome Measure(s) : ?Before the interventions, participants were pretested by completing the figure-8 hop test for time, the triple-crossover hop test for distance, isometric strength tests (dorsiflexion, plantar flexion, inversion, and eversion), the Y-Balance test, and the visual analog scale for perceived ankle instability. Participants were again tested 6 weeks later. We conducted 2 separate, multivariate, repeated-measures analyses of variance, followed by univariate analyses on any significant findings. Results : ?The resistance-band protocol group improved in strength (dorsiflexion, inversion, and eversion) and on the visual analog scale (P < .05); the proprioceptive neuromuscular facilitation group improved in strength (inversion and eversion) and on the visual analog scale (P < .05) as well. No improvements were seen in the triple-crossover hop or the Y-Balance tests for either intervention group or in the control group for any dependent variable (P > .05). Conclusions : ?Although the resistance-band protocol is common in rehabilitation, the proprioceptive neuromuscular facilitation strength protocol is also an effective treatment to improve strength in individuals with CAI. Both protocols showed clinical benefits in strength and perceived instability. To improve functional outcomes, clinicians should consider using additional multiplanar and multijoint exercises.
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Families Parenting Adolescents With Substance Abuse-Recovering the Mother's Voice: A Narrative Literature Review.
J Fam Nurs
PUBLISHED: 10-23-2014
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Alcohol and substance dependency are complex, problematic phenomena, which are growing worldwide. In particular, drug use and abuse among young people is a significant concern. Although addiction presents as a problem of dependent individuals, families are also profoundly affected by the family member's addiction. In this narrative literature review, we review published research from 1937 to 2014 to capture a narrative and historical perspective of addiction and family. We condense and analyze the experiences of parents with alcohol- and drug-dependent children, to emphasize the need for a more specific, in-depth exploration of mothers' experiences. Such exploration may advance nurses' understandings of individual, familial, and social complexities of parenting an addicted child.
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Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers.
Paolo Peterlongo, Jenny Chang-Claude, Kirsten B Moysich, Anja Rudolph, Rita K Schmutzler, Jacques Simard, Penny Soucy, Rosalind A Eeles, Douglas F Easton, Ute Hamann, Stefan Wilkening, Bowang Chen, Matti A Rookus, Marjanka K Schmidt, Frederieke H van der Baan, Amanda B Spurdle, Logan C Walker, Felicity Lose, Ana-Teresa Maia, Marco Montagna, Laura Matricardi, Jan Lubiński, Anna Jakubowska, Encarna B Gomez-Garcia, Olufunmilayo I Olopade, Robert L Nussbaum, Katherine L Nathanson, Susan M Domchek, Timothy R Rebbeck, Banu K Arun, Beth Y Karlan, Sandra Orsulic, Jenny Lester, Wendy K Chung, Alex Miron, Melissa C Southey, David E Goldgar, Saundra S Buys, Ramunas Janavicius, Cecelia M Dorfling, Elizabeth J van Rensburg, Yuan Chun Ding, Susan L Neuhausen, Thomas V O Hansen, Anne-Marie Gerdes, Bent Ejlertsen, Lars Jønson, Ana Osorio, Cristina Martinez-Bouzas, Javier Benitez, Edye E Conway, Kathleen R Blazer, Jeffrey N Weitzel, Siranoush Manoukian, Bernard Peissel, Daniela Zaffaroni, Giulietta Scuvera, Monica Barile, Filomena Ficarazzi, Frederique Mariette, Stefano Fortuzzi, Alessandra Viel, Giuseppe Giannini, Laura Papi, Aline Martayan, Maria Grazia Tibiletti, Paolo Radice, Athanassios Vratimos, Florentia Fostira, Judy E Garber, Alan Donaldson, Carole Brewer, Claire Foo, D Gareth R Evans, Debra Frost, Diana Eccles, Angela Brady, Jackie Cook, Marc Tischkowitz, Julian Adlard, Julian Barwell, Lisa Walker, Louise Izatt, Lucy E Side, M John Kennedy, Mark T Rogers, Mary E Porteous, Patrick J Morrison, Radka Platte, Rosemarie Davidson, Shirley V Hodgson, Steve Ellis, Trevor Cole, Andrew K Godwin, Kathleen Claes, Tom Van Maerken, Alfons Meindl, Andrea Gehrig, Christian Sutter, Christoph Engel, Dieter Niederacher, Doris Steinemann, Hansjoerg Plendl, Karin Kast, Kerstin Rhiem, Nina Ditsch, Norbert Arnold, Raymonda Varon-Mateeva, Barbara Wappenschmidt, Shan Wang-Gohrke, Brigitte Bressac-de Paillerets, Bruno Buecher, Capucine Delnatte, Claude Houdayer, Dominique Stoppa-Lyonnet, Francesca Damiola, Isabelle Coupier, Laure Barjhoux, Laurence Venat-Bouvet, Lisa Golmard, Nadia Boutry-Kryza, Olga M Sinilnikova, Olivier Caron, Pascal Pujol, Sylvie Mazoyer, Muriel Belotti, Marion Piedmonte, Michael L Friedlander, Gustavo C Rodriguez, Larry J Copeland, Miguel de la Hoya, Pedro Perez Segura, Heli Nevanlinna, Kristiina Aittomäki, Theo A M van Os, Hanne E J Meijers-Heijboer, Annemarie H Van der Hout, Maaike P G Vreeswijk, Nicoline Hoogerbrugge, Margreet G E M Ausems, Helena C Van Doorn, J Margriet Collée, Edith Olah, Orland Díez, Ignacio Blanco, Conxi Lazaro, Joan Brunet, Lídia Feliubadaló, Cezary Cybulski, Jacek Gronwald, Katarzyna Durda, Katarzyna Jaworska-Bieniek, Grzegorz Sukiennicki, Adalgeir Arason, Jocelyne Chiquette, Manuel R Teixeira, Curtis Olswold, Fergus J Couch, Noralane M Lindor, Xianshu Wang, Csilla I Szabo, Kenneth Offit, Marina Corines, Lauren Jacobs, Mark Robson, Liying Zhang, Vijai Joseph, Andreas Berger, Christian F Singer, Christine Rappaport, Daphne Geschwantler Kaulich, Georg Pfeiler, Muy-Kheng M Tea, Catherine M Phelan, Mark H Greene, Phuong L Mai, Gad Rennert, Anna Marie Mulligan, Gord Glendon, Sandrine Tchatchou, Irene L Andrulis, Amanda Ewart Toland, Anders Bojesen, Inge Sokilde Pedersen, Mads Thomassen, Uffe Birk Jensen, Yael Laitman, Johanna Rantala, Anna von Wachenfeldt, Hans Ehrencrona, Marie Stenmark Askmalm, Ake Borg, Karoline B Kuchenbaecker, Lesley McGuffog, Daniel Barrowdale, Sue Healey, Andrew Lee, Paul D P Pharoah, Georgia Chenevix-Trench, Antonis C Antoniou, Eitan Friedman.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 10-23-2014
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Background: BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and non-genetic modifying factors. In this study we evaluated the putative role of variants in many candidate modifier genes. Methods: Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n=3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach. Results: The observed p-values of association ranged between 0.005-1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments. Conclusion: There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers. Impact: Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies.
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The role of government policy in service development in a New Zealand statutory mental health service: implications for policy planning and development.
Australas Psychiatry
PUBLISHED: 10-21-2014
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To explore the relationship between government policy and service development in a New Zealand statutory mental health provider, Living Well.
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Best practice guidelines on publishing ethics: a publisher's perspective, 2nd edition.
Ann. N. Y. Acad. Sci.
PUBLISHED: 10-21-2014
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Wiley has updated its publishing ethics guidelines, first published in 2006. The new guidelines provide guidance, resources, and practical advice on ethical concerns that arise in academic publishing for editors, authors, and researchers, among other audiences. New guidance is also included on whistle blowers, animal research, clinical research, and clinical trial registration, addressing cultural differences, human rights, and confidentiality. The guidelines are uniquely interdisciplinary and were reviewed by 24 editors and experts chosen from the wide range of communities that Wiley serves. The new guidelines are also published in Advanced Materials, Headache, International Journal of Clinical Practice, Social Science Quarterly, and on the website http://exchanges.wiley.com/ethicsguidelines.
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Preliminary Results of a Phase II Trial of Proton Radiotherapy for Pediatric Rhabdomyosarcoma.
J. Clin. Oncol.
PUBLISHED: 10-20-2014
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This prospective phase II study was designed to assess disease control and to describe acute and late adverse effects of treatment with proton radiotherapy in children with rhabdomyosarcoma (RMS).
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Correlations Between Sexual Abuse Histories, Perceived Danger, and PTSD Among Intimate Partner Violence Victims.
J Interpers Violence
PUBLISHED: 10-18-2014
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Intimate partner violence (IPV), childhood abuse, and sexual assault in adulthood are profound public health concerns, particularly for women. Exposure to trauma can contribute to long-standing health problems and escalated medical costs. Unfortunately, these experiences are often intertwined. Sexual assault often occurs in intimate relationships in which there is concurrent IPV; likewise, many victims of IPV have experienced childhood abuse. The prevalent intersections of these struggles can lead to posttraumatic stress disorder (PTSD) symptoms. This article examines the contributions of childhood abuse histories and sexual assault to PTSD symptoms among women experiencing IPV. Findings suggest childhood abuse experiences account for more variance in PTSD symptoms than adult sexual assault. Clinical implications are discussed.
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A community lifeline and point of contact.
Nurs Stand
PUBLISHED: 10-16-2014
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Since becoming chief executive of the Nursing and Midwifery Council I have wanted to find out more about what it is like to deliver care as a nurse or midwife in the UK.
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Development and Validation of the Dyspnea Index (DI): A Severity Index for Upper Airway-Related Dyspnea.
J Voice
PUBLISHED: 10-15-2014
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To (1) develop and validate the Dyspnea Index (DI); (2) quantify severity of symptoms in upper airway dyspnea; and (3) validate the DI as an outcome measure.
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Self-reported quality of life of adolescents with cerebral palsy: a cross-sectional and longitudinal analysis.
Lancet
PUBLISHED: 10-11-2014
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Children with cerebral palsy who can self-report have similar quality of life (QoL) to their able-bodied peers. Is this similarity also found in adolescence? We examined how self-reported QoL of adolescents with cerebral palsy varies with impairment and compares with the general population, and how factors in childhood predict adolescent QoL.
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Exploring Electronic Health Records as a Population Health Surveillance Tool of Cardiovascular Disease Risk Factors.
Popul Health Manag
PUBLISHED: 10-08-2014
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Abstract The objective of this study was to examine the utility of using electronic health record (EHR) data for periodic community health surveillance of cardiovascular disease (CVD) risk factors through 2 research questions. First, how many years of EHR data are needed to produce reliable estimates of key population-level CVD health indicators for a community? Second, how comparable are the EHR estimates relative to those from community screenings? The study takes place in the context of the Heart of New Ulm Project, a 10-year population health initiative designed to reduce myocardial infarctions and CVD risk factor burden in a rural community. The community is served by 1 medical center that includes a clinic and hospital. The project screened adult residents of New Ulm for CVD risk factors in 2009. EHR data for 3 years prior to the heart health screenings were extracted for patients from the community. Single- and multiple-year EHR prevalence estimates were compared for individuals ages 40-79 years (N=5918). EHR estimates also were compared to screening estimates (N=3123). Single-year compared with multiyear EHR data prevalence estimates were sufficiently precise for this rural community. EHR and screening prevalence estimates differed significantly-systolic blood pressure (BP) (124.0 vs. 128.9), diastolic BP (73.3 vs. 79.2), total cholesterol (186.0 vs. 201.0), body mass index (30.2 vs. 29.5), and smoking (16.6% vs. 8.2%)-suggesting some selection bias depending on the method used. Despite differences between data sources, EHR data may be a useful source of population health surveillance to inform and evaluate local population health initiatives. (Population Health Management 2014;xx:xxx-xxx).
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Clinical significance of autoantibodies in a large cohort of patients with chronic graft-versus-host disease defined by NIH criteria.
Am. J. Hematol.
PUBLISHED: 09-22-2014
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There is an unmet need for identifying new clinical biomarkers in chronic Graft-versus-Host-disease (cGVHD) suitable for diagnosis and disease monitoring. Circulating autoantibodies represent an ongoing immune response and suggest a pathogenic role for B cells in cGVHD. Autoantibodies could be useful markers of cGVHD disease activity, severity or organ specificity; however, their clinical utility is not established. The focus of this study was to determine the incidence and associations of a broad array of clinical autoantibodies with cGVHD manifestations in a large patient cohort characterized by NIH criteria. A panel of 21 circulating antibodies commonly used in clinical medicine was tested in 280 cGVHD patients (70% severe) enrolled in a cross-sectional prospective natural history study. Median cGVHD duration was two years. Patients with circulating autoantibodies (62%) had significantly higher levels of IgM (p<.0001), IgG (p<.0001) and IgA (p=.001), elevated uric acid (p=.008) and total protein (p=.0004), and higher numbers of CD3+ (p=.002), CD4+ (p=.001), CD8+ (p=.023) T cells and CD19+ B cells (p<.0001). Multiple antibodies were detected in 35% of patients. Prior rituximab therapy (n=66) was associated with reduced presence of autoantibodies (48 vs. 66% p=.01). Only oral cGVHD was significantly associated with presence of autoantibodies in this study (p=.028) No significant associations were found between cGVHD activity and severity, and presence of autoantibodies. Circulating autoantibodies are common in patients with advanced cGVHD. Their presence is associated with better quantitative immunologic reconstitution but does not have utility as a clinical biomarker of cGVHD.
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The support needs of new graduate nurses making the transition to rural nursing practice in Australia.
J Clin Nurs
PUBLISHED: 09-10-2014
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The aim of this paper is to present the findings from the new graduate nurse participants of a larger study that explored the transitional experiences of newly graduated nurses making the role transition in rural health care facilities in Australia.
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Best Practice Guidelines on Publishing Ethics: A Publisher's Perspective, 2nd Edition.
Adv. Mater. Weinheim
PUBLISHED: 08-27-2014
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Wiley has updated its publishing ethics guidelines, first published in 2006. These new guidelines provide guidance, resources, and practical advice on ethical concerns that arise in academic publishing for editors, authors, and researchers, among other audiences. New guidance is included about whistle blowers, animal research, clinical research, and clinical trial registration, addressing cultural differences, human rights, and confidentiality. The guidelines are uniquely interdisciplinary, and were reviewed by 24 editors and experts chosen from the wide range of communities that Wiley serves. These guidelines are also published in: Headache, International Journal of Clinical Practice, Annals of the New York Academy of Sciences, Social Science Quarterly, and on the website http://exchanges.wiley.com/ethicsguidelines.
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The Elaborated Intrusion Theory of desire: A 10-year retrospective and implications for addiction treatments.
Addict Behav
PUBLISHED: 08-26-2014
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Introduction: Ten years after the publication of Elaborated Intrusion (EI) Theory, there is now substantial research into its key predictions. The distinction between intrusive thoughts, which are driven by automatic processes, and their elaboration, involving controlled processing, is well established. Desires for both addictive substances and other desired targets are typically marked by imagery, especially when they are intense. Attention training strategies such as body scanning reduce intrusive thoughts, while concurrent tasks that introduce competing sensory information interfere with elaboration, especially if they compete for the same limited-capacity working memory resources. Conclusion: EI Theory has spawned new assessment instruments that are performing strongly and offer the ability to more clearly delineate craving from correlated processes. It has also inspired new approaches to treatment. In particular, training people to use vivid sensory imagery for functional goals holds promise as an intervention for substance misuse, since it is likely to both sustain motivation and moderate craving.
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Best Practice Guidelines on Publishing Ethics: A Publisher's Perspective, 2nd Edition.
Headache
PUBLISHED: 08-22-2014
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Wiley has updated its publishing ethics guidelines, first published in 2006. The new guidelines provide guidance, resources, and practical advice on ethical concerns that arise in academic publishing for editors, authors, and researchers, among other audiences. New guidance is also included on whistle blowers, animal research, clinical research, and clinical trial registration, addressing cultural differences, human rights, and confidentiality. The guidelines are uniquely interdisciplinary, and were reviewed by 24 editors and experts chosen from the wide range of communities that Wiley serves. They are also published in Advanced Materials, International Journal of Clinical Practice, Annals of the New York Academy of Sciences, Social Science Quarterly, and on the website http://exchanges.wiley.com/ethicsguidelines.
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Stress- and diet-induced fat gain is controlled by NPY in catecholaminergic neurons.
Mol Metab
PUBLISHED: 08-01-2014
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Neuropeptide Y (NPY) and noradrenaline are commonly co-expressed in sympathetic neurons. Both are key regulators of energy homeostasis and critical for stress-coping. However, little is known about the specific function of NPY in the catecholaminergic system in these regulations. Here we show that mice with NPY expression only in the noradrenergic and adrenergic cells of the catecholaminergic system (catNPY) exhibited exacerbated diet-induced obesity, lower body and brown adipose tissue temperatures compared to WT and NPY(-/-) mice under a HFD. Furthermore, chronic stress increased adiposity and serum corticosterone level in WT but not NPY(-/-) mice. Re-introducing NPY specifically to the catecholaminergic system in catNPY mice restored stress responsiveness associated with increased respiratory exchange ratio and decreased liver pACC to tACC ratio. These results demonstrate catecholaminergic NPY signalling is critical in mediating diet- and chronic stress-induced fat gain via effects on diet-induced thermogenesis and stress-induced increases in corticosterone levels and lipogenic capacity.
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Uncovering Methods for the Prevention of Protein Aggregation and Improvement of Product Quality in a Transient Expression System.
Biotechnol. Prog.
PUBLISHED: 07-29-2014
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Mammalian expression systems are used routinely for the production of recombinant proteins as therapeutic molecules as well as research tools. Transient expression has become increasingly popular in recent years due to its rapid timeline and improvements in expression level. While improvements to transient expression systems have focused mainly on the level of protein expression, the aspect of protein quality has received little attention. The removal of undesirable products, such as aggregation, depends primarily on purification, requiring additional cumbersome steps, which can lead to a lower product yield and longer timelines. In this study, we show that reducing the level of transcription by transfecting at a lower gene dose improves the quality of secreted molecules prone to aggregation. For gene dosing to have this effect, it is critical for the carrier DNA to be an empty vector containing the same elements as the gene containing plasmid. This approach can be used in combination with a temperature shift to hypothermic conditions during production to enhance the effect. The observed improvements not only minimized aggregation levels, but also generated products with overall superior quality, including more homogeneous signal peptide cleavage and N-linked glycosylation profiles. These techniques have produced a similar improvement in product quality with a variety of other molecules, suggesting that this may be a general approach to enhance product quality from transient expression systems. This article is protected by copyright. All rights reserved.
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Quality of life outcomes in proton and photon treated pediatric brain tumor survivors.
Radiother Oncol
PUBLISHED: 06-24-2014
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Radiotherapy can impair Health Related Quality of Life (HRQoL) in survivors of childhood brain tumors, but proton radiotherapy (PRT) may mitigate this effect. This study compares HRQoL in PRT and photon (XRT) pediatric brain tumor survivors.
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Delaying chemoradiation until after completion of adjuvant chemotherapy for pancreatic cancer may not impact local control.
Pract Radiat Oncol
PUBLISHED: 06-04-2014
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Timing of administration of adjuvant chemoradiation (CRT) for pancreatic cancer has varied across studies. To date, the impact of timing of adjuvant CRT on long-term outcomes has not been evaluated. This study evaluates the effect of timing of adjuvant CRT on locoregional control (LRC) and overall survival (OS).
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DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers.
Ana Osorio, Roger L Milne, Karoline Kuchenbaecker, Tereza Vaclová, Guillermo Pita, Rosario Alonso, Paolo Peterlongo, Ignacio Blanco, Miguel de la Hoya, Mercedes Durán, Orland Díez, Teresa Ramón Y Cajal, Irene Konstantopoulou, Cristina Martinez-Bouzas, Raquel Andrés Conejero, Penny Soucy, Lesley McGuffog, Daniel Barrowdale, Andrew Lee, Swe-Brca, Brita Arver, Johanna Rantala, Niklas Loman, Hans Ehrencrona, Olufunmilayo I Olopade, Mary S Beattie, Susan M Domchek, Katherine Nathanson, Timothy R Rebbeck, Banu K Arun, Beth Y Karlan, Christine Walsh, Jenny Lester, Esther M John, Alice S Whittemore, Mary B Daly, Melissa Southey, John Hopper, Mary B Terry, Saundra S Buys, Ramunas Janavicius, Cecilia M Dorfling, Elizabeth J van Rensburg, Linda Steele, Susan L Neuhausen, Yuan Chun Ding, Thomas V O Hansen, Lars Jønson, Bent Ejlertsen, Anne-Marie Gerdes, Mar Infante, Belen Herráez, Leticia Thais Moreno, Jeffrey N Weitzel, Josef Herzog, Kisa Weeman, Siranoush Manoukian, Bernard Peissel, Daniela Zaffaroni, Giulietta Scuvera, Bernardo Bonanni, Frederique Mariette, Sara Volorio, Alessandra Viel, Liliana Varesco, Laura Papi, Laura Ottini, Maria Grazia Tibiletti, Paolo Radice, Drakoulis Yannoukakos, Judy Garber, Steve Ellis, Debra Frost, Radka Platte, Elena Fineberg, Gareth Evans, Fiona Lalloo, Louise Izatt, Ros Eeles, Julian Adlard, Rosemarie Davidson, Trevor Cole, Diana Eccles, Jackie Cook, Shirley Hodgson, Carole Brewer, Marc Tischkowitz, Fiona Douglas, Mary Porteous, Lucy Side, Lisa Walker, Patrick Morrison, Alan Donaldson, John Kennedy, Claire Foo, Andrew K Godwin, Rita Katharina Schmutzler, Barbara Wappenschmidt, Kerstin Rhiem, Christoph Engel, Alfons Meindl, Nina Ditsch, Norbert Arnold, Hans Jörg Plendl, Dieter Niederacher, Christian Sutter, Shan Wang-Gohrke, Doris Steinemann, Sabine Preisler-Adams, Karin Kast, Raymonda Varon-Mateeva, Andrea Gehrig, Dominique Stoppa-Lyonnet, Olga M Sinilnikova, Sylvie Mazoyer, Francesca Damiola, Bruce Poppe, Kathleen Claes, Marion Piedmonte, Kathy Tucker, Floor Backes, Gustavo Rodriguez, Wendy Brewster, Katie Wakeley, Thomas Rutherford, Trinidad Caldés, Heli Nevanlinna, Kristiina Aittomäki, Matti A Rookus, Theo A M van Os, Lizet van der Kolk, J L de Lange, Hanne E J Meijers-Heijboer, A H van der Hout, Christi J van Asperen, Encarna B Gomez Garcia, Nicoline Hoogerbrugge, J Margriet Collée, Carolien H M van Deurzen, Rob B van der Luijt, Peter Devilee, Hebon, Edith Olah, Conxi Lazaro, Alex Teulé, Mireia Menéndez, Anna Jakubowska, Cezary Cybulski, Jacek Gronwald, Jan Lubiński, Katarzyna Durda, Katarzyna Jaworska-Bieniek, Oskar Th Johannsson, Christine Maugard, Marco Montagna, Silvia Tognazzo, Manuel R Teixeira, Sue Healey, Kconfab Investigators, Curtis Olswold, Lucia Guidugli, Noralane Lindor, Susan Slager, Csilla I Szabo, Joseph Vijai, Mark Robson, Noah Kauff, Liying Zhang, Rohini Rau-Murthy, Anneliese Fink-Retter, Christian F Singer, Christine Rappaport, Daphne Geschwantler Kaulich, Georg Pfeiler, Muy-Kheng Tea, Andreas Berger, Catherine M Phelan, Mark H Greene, Phuong L Mai, Flavio Lejbkowicz, Irene Andrulis, Anna Marie Mulligan, Gord Glendon, Amanda Ewart Toland, Anders Bojesen, Inge Sokilde Pedersen, Lone Sunde, Mads Thomassen, Torben A Kruse, Uffe Birk Jensen, Eitan Friedman, Yael Laitman, Shani Paluch Shimon, Jacques Simard, Douglas F Easton, Kenneth Offit, Fergus J Couch, Georgia Chenevix-Trench, Antonis C Antoniou, Javier Benitez.
PLoS Genet.
PUBLISHED: 04-01-2014
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Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7 × 10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8 × 10(-3)). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.
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Program participation and blood pressure improvement in the Heart of New Ulm Project, Minnesota, 2009-2011.
Prev Chronic Dis
PUBLISHED: 03-29-2014
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The Heart of New Ulm (HONU) Project is a community-based heart disease prevention intervention that delivers various component programs through health care, work sites, and the community. We examined the association between HONU program participation and blood pressure (BP) control over the first 2 years of the project.
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Prognostic significance of treatment-induced pathologic necrosis in extremity and truncal soft tissue sarcoma after neoadjuvant chemoradiotherapy.
Cancer
PUBLISHED: 03-23-2014
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Histologic response to chemotherapy has been shown to be an independent prognostic factor in patients with osteosarcoma and Ewing sarcoma. However, in patients with soft tissue sarcoma (STS), the prognostic impact of histologic response to chemotherapy is less clear. In the current study, the authors sought to determine the prognostic significance of treatment-induced pathologic necrosis in patients receiving neoadjuvant chemoradiotherapy for STS.
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Genetic mechanisms in interval colon cancers.
Dig. Dis. Sci.
PUBLISHED: 03-23-2014
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The factors underlying the development of interval colon cancers are not well defined and are likely heterogeneous. We sought to determine whether there are distinct molecular properties associated with interval colon cancers.
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A pilot study of telepractice delivery for teaching listening and spoken language to children with hearing loss.
J Telemed Telecare
PUBLISHED: 03-18-2014
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Telemedicine ("telepractice") allows improved access to specialised early intervention services such as Auditory-Verbal Therapy (AVT) for children with hearing loss. We investigated the effectiveness of a tele-AVT programme (eAVT) in the spoken language development of a group of young children with hearing loss. In a retrospective study we compared the language outcomes of children with bilateral hearing loss receiving eAVT with a control group who received therapy In Person. Seven children in each group (mean age 2.4 years) were matched on pre-amplification hearing level for the better hearing ear, age at optimal amplification and enrolment in the AVT programme. The eAVT sessions were conducted via Skype. Results on the Preschool Language Scale-4 were compared at 2 years post optimal amplification. There were no significant differences in language scores between the two groups. Language scores for the children in the eAVT group were within the normal range for children with normal hearing. The results suggest that early intervention AVT via telepractice may be as effective as delivery In Person for children with hearing loss.
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Economic and comorbidity burden among moderate-to-severe psoriasis patients with comorbid psoriatic arthritis.
Arthritis Care Res (Hoboken)
PUBLISHED: 03-11-2014
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Objective: To compare the prevalence of comorbidities, healthcare utilization and costs between moderate-to-severe psoriasis (PsO) patients with comorbid psoriatic arthritis (PsA) and matched controls. Methods: Adults aged 18 to 64 years with concomitant diagnoses of PsO and PsA (PsO+PsA) were identified in the OptumHealth Reporting and Insights claims database between January 2007 and March 2012. Moderate-to-severe PsO was defined based on the use of at least one systemic or phototherapy during the 12-month study period after the index date (randomly selected date after the first PsO diagnosis). Control patients without PsO and PsA were demographically matched 1:1 with PsO+PsA patients. Multivariate regressions were employed to examine PsO/PsA-related comorbidities, medications, healthcare utilization and costs between PsO+PsA patients and controls, adjusting for demographics, index year, insurance type, and non-PsO/PsA related comorbidities. Results: Among 1,230 matched pairs of PsO+PsA patients and controls, PsO+PsA patients had significantly more PsO/PsA-related comorbidities, with the top three most common in both groups being hypertension (35.8% vs. 23.5%), hyperlipidemia (34.6% vs. 28.5%), and diabetes (15.9% vs. 10.0%). Compared with controls, PsO+PsA patients had a higher number of distinct prescriptions filled (incidence rate ratio=2.3), were more likely to have inpatient admissions (odds ratio (OR)=1.6), emergency room visits (OR=1.3) and outpatient visits (OR=62.7) (all p<0.05), and incurred significantly higher total, pharmacy, and medical costs (adjusted annual cost differences per patient: $23,160, $17,696, and $5,077, respectively, all p<0.01). Conclusions: Compared with matched PsO- and PsA-free controls, moderate-to-severe PsO patients with comorbid PsA had higher comorbidity and healthcare utilization and costs. © 2014 American College of Rheumatology.
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Can virtual nature improve patient experiences and memories of dental treatment? A study protocol for a randomized controlled trial.
Trials
PUBLISHED: 03-11-2014
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Dental anxiety and anxiety-related avoidance of dental care create significant problems for patients and the dental profession. Distraction interventions are used in daily medical practice to help patients cope with unpleasant procedures. There is evidence that exposure to natural scenery is beneficial for patients and that the use of virtual reality (VR) distraction is more effective than other distraction interventions, such as watching television. The main aim of this randomized controlled trial is to determine whether the use of VR during dental treatment can improve the overall dental experience and recollections of treatment for patients, breaking the negative cycle of memories of anxiety leading to further anxiety, and avoidance of future dental appointments. Additionally, the aim is to test whether VR benefits dental patients with all levels of dental anxiety or whether it could be especially beneficial for patients suffering from higher levels of dental anxiety. The third aim is to test whether the content of the VR distraction can make a difference for its effectiveness by comparing two types of virtual environments, a natural environment and an urban environment.
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Assessing the food environment of a rural community: baseline findings from the heart of New Ulm project, Minnesota, 2010-2011.
Prev Chronic Dis
PUBLISHED: 03-08-2014
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Changes in the food environment in the United States during the past few decades have contributed to increased rates of obesity, diabetes, and heart disease. Improving the food environment may be an effective primary prevention strategy to address these rising disease rates. The purpose of this study was to assess the consumer food environment of a rural community with high rates of obesity and low levels of fruit and vegetable consumption. Findings were used to identify food environment intervention strategies to be implemented as part of a larger community-based heart disease prevention program.
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Wnt-3a activated human fibroblasts promote human keratinocyte proliferation and matrix destruction.
Int. J. Cancer
PUBLISHED: 02-28-2014
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Aberrant Wnt regulation, detectable by nuclear translocation of Beta-catenin, is a hallmark of many cancers including skin squamous cell carcinomas (SCCs). By analyzing primary human skin SCCs, we demonstrate that nuclear Beta-catenin is not restricted to SCC cells but also detected in stromal fibroblasts, suggesting an important role for aberrant Wnt regulation also in the tumor microenvironment. When human keratinocytes and fibroblasts were treated with Wnt-3a, fibroblasts proved to be more responsive. Accordingly, Wnt-3a did not alter HaCaT cell functions in a cell-autonomous manner. However, when organotypic cultures (OTCs) were treated with Wnt-3a, HaCaT keratinocytes responded with increased proliferation. As nuclear Beta-catenin was induced only in the fibroblasts, this argued for a Wnt-dependent, paracrine keratinocyte stimulation. Global gene expression analysis of Wnt-3a-stimulated fibroblasts identified genes encoding Interleukin-8 (IL-8) and C-C motif chemokine 2 (CCL-2) as well as Matrix metalloproteinase-1 (MMP-1) as Wnt-3a targets. In agreement, we show that IL-8 and CCL-2 were secreted in high amounts by Wnt-3a-stimulated fibroblasts also in OTCs. The functional role of IL-8 and CCL-2 as keratinocyte growth regulators was confirmed by directly stimulating HaCaT cell proliferation in conventional cultures. Most important, neutralizing antibodies against IL-8 and CCL-2 abolished the Wnt-dependent HaCaT cell hyperproliferation in OTCs. Additionally, MMP-1 was expressed in high amounts in Wnt-3a-stimulated OTCs and degraded the stromal matrix. Thus, our data show that Wnt-3a stimulates fibroblasts to secrete both keratinocyte proliferation-inducing cytokines and stroma-degrading metalloproteinases, thereby providing evidence for a novel Wnt deregulation in the tumor-stroma directly contributing to skin cancer progression. This article is protected by copyright. All rights reserved.
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Ethanol locks in the prevention and treatment of catheter-related bloodstream infections.
Ann Pharmacother
PUBLISHED: 02-19-2014
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To evaluate the evidence regarding the use of ethanol lock therapy (ELT) for catheter-related bloodstream infection (CRBSI) prophylaxis and treatment.
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The Craving Experience Questionnaire: a brief, theory-based measure of consummatory desire and craving.
Addiction
PUBLISHED: 02-16-2014
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Research into craving is hampered by lack of theoretical specification and a plethora of substance-specific measures. This study aimed to develop a generic measure of craving based on elaborated intrusion (EI) theory. Confirmatory factor analysis (CFA) examined whether a generic measure replicated the three-factor structure of the Alcohol Craving Experience (ACE) scale over different consummatory targets and time-frames.
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Mutational analysis and clinical correlation of metastatic colorectal cancer.
Cancer
PUBLISHED: 02-05-2014
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Early identification of mutations may guide patients with metastatic colorectal cancer toward targeted therapies that may be life prolonging. The authors assessed tumor genotype correlations with clinical characteristics to determine whether mutational profiling can account for clinical similarities, differences, and outcomes.
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Head-to-head comparison of serial soluble ST2, growth differentiation factor-15, and highly-sensitive troponin T measurements in patients with chronic heart failure.
JACC Heart Fail
PUBLISHED: 01-25-2014
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This analysis aimed to perform a head-to-head comparison of 3 of the promising biomarkers of cardiovascular (CV) outcomes in heart failure (HF)-soluble ST2 (sST2), growth differentiation factor (GDF)-15, and highly-sensitive troponin T (hsTnT)-and to evaluate the role of serial measurement of these biomarkers in patients with chronic HF.
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Playing 'Tetris' reduces the strength, frequency and vividness of naturally occurring cravings.
Appetite
PUBLISHED: 01-23-2014
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Elaborated Intrusion Theory (EI) postulates that imagery is central to craving, therefore a visually based task should decrease craving and craving imagery. This study provides the first laboratory test of this hypothesis in naturally occurring, rather than artificially induced, cravings. Participants reported if they were experiencing a craving and rated the strength, vividness and intrusiveness of their craving. They then either played 'Tetris' or they waited for a computer program to load (they were told it would load, but it was designed not to). Before task completion, craving scores between conditions did not differ; after, however, participants who had played 'Tetris' had significantly lower craving and less vivid craving imagery. The findings support EI theory, showing that a visuospatial working memory load reduces naturally occurring cravings, and that Tetris might be a useful task for tackling cravings outside the laboratory. Methodologically, the findings show that craving can be studied in the laboratory without using craving induction procedures.
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Pancreatic polypeptide controls energy homeostasis via Npy6r signaling in the suprachiasmatic nucleus in mice.
Cell Metab.
PUBLISHED: 01-14-2014
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Y-receptors control energy homeostasis, but the role of Npy6 receptors (Npy6r) is largely unknown. Young Npy6r-deficient (Npy6r(-/-)) mice have reduced body weight, lean mass, and adiposity, while older and high-fat-fed Npy6r(-/-) mice have low lean mass with increased adiposity. Npy6r(-/-) mice showed reduced hypothalamic growth hormone releasing hormone (Ghrh) expression and serum insulin-like growth factor-1 (IGF-1) levels relative to WT. This is likely due to impaired vasoactive intestinal peptide (VIP) signaling in the suprachiasmatic nucleus (SCN), where we found Npy6r coexpressed in VIP neurons. Peripheral administration of pancreatic polypeptide (PP) increased Fos expression in the SCN, increased energy expenditure, and reduced food intake in WT, but not Npy6r(-/-), mice. Moreover, intraperitoneal (i.p.) PP injection increased hypothalamic Ghrh mRNA expression and serum IGF-1 levels in WT, but not Npy6r(-/-), mice, an effect blocked by intracerebroventricular (i.c.v.) Vasoactive Intestinal Peptide (VPAC) receptors antagonism. Thus, PP-initiated signaling through Npy6r in VIP neurons regulates the growth hormone axis and body composition.
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Targeted Prostate Cancer Screening in BRCA1 and BRCA2 Mutation Carriers: Results from the Initial Screening Round of the IMPACT Study.
Elizabeth K Bancroft, Elizabeth C Page, Elena Castro, Hans Lilja, Andrew Vickers, Daniel Sjoberg, Melissa Assel, Christopher S Foster, Gillian Mitchell, Kate Drew, Lovise Mæhle, Karol Axcrona, D Gareth Evans, Barbara Bulman, Diana Eccles, Donna McBride, Christi van Asperen, Hans Vasen, Lambertus A Kiemeney, Janneke Ringelberg, Cezary Cybulski, Dominika Wokolorczyk, Christina Selkirk, Peter J Hulick, Anders Bojesen, Anne-Bine Skytte, Jimmy Lam, Louise Taylor, Rogier Oldenburg, Ruben Cremers, Gerald Verhaegh, Wendy A van Zelst-Stams, Jan C Oosterwijk, Ignacio Blanco, Mónica Salinas, Jackie Cook, Derek J Rosario, Saundra Buys, Tom Conner, Margreet G Ausems, Kai-Ren Ong, Jonathan Hoffman, Susan Domchek, Jacquelyn Powers, Manuel R Teixeira, Sofia Maia, William D Foulkes, Nassim Taherian, Mariëlle Ruijs, Apollonia T Helderman-van den Enden, Louise Izatt, Rosemarie Davidson, Muriel A Adank, Lisa Walker, Rita Schmutzler, Kathy Tucker, Judy Kirk, Shirley Hodgson, Marion Harris, Fiona Douglas, Geoffrey J Lindeman, Janez Zgajnar, Marc Tischkowitz, Virginia E Clowes, Rachel Susman, Teresa Ramón Y Cajal, Nicholas Patcher, Neus Gadea, Allan Spigelman, Theo van Os, Annelie Liljegren, Lucy Side, Carole Brewer, Angela F Brady, Alan Donaldson, Vigdis Stefansdottir, Eitan Friedman, Rakefet Chen-Shtoyerman, David J Amor, Lucia Copáková, Julian Barwell, Veda N Giri, Vedang Murthy, Nicola Nicolai, Soo-Hwang Teo, Lynn Greenhalgh, Sara Strom, Alex Henderson, John McGrath, David Gallagher, Neil Aaronson, Audrey Ardern-Jones, Chris Bangma, David Dearnaley, Philandra Costello, Jorunn Eyfjord, Jeanette Rothwell, Alison Falconer, Henrik Grönberg, Freddie C Hamdy, Oskar Johannsson, Vincent Khoo, Zsofia Kote-Jarai, Jan Lubiński, Ulrika Axcrona, Jane Melia, Joanne McKinley, Anita V Mitra, Clare Moynihan, Gad Rennert, Mohnish Suri, Penny Wilson, Emma Killick, , Sue Moss, Rosalind A Eeles.
Eur. Urol.
PUBLISHED: 01-02-2014
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Men with germline breast cancer 1, early onset (BRCA1) or breast cancer 2, early onset (BRCA2) gene mutations have a higher risk of developing prostate cancer (PCa) than noncarriers. IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls) is an international consortium of 62 centres in 20 countries evaluating the use of targeted PCa screening in men with BRCA1/2 mutations.
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Intravesical instillation of pentosan polysulfate encapsulated in a liposome nanocarrier for interstitial cystitis.
Am J Clin Exp Urol
PUBLISHED: 01-01-2014
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We determined the effect of intravesical instillation of pentosan polysulfate encapsulated in liposomes for refractory interstitial cystitis patients. This was an open label uncontrolled study. Subjects were recruited from a private urology practice. Inclusion criteria included patients who met NIDDK criteria for Interstitial Cystitis (IC) and who were responding poorly to conventional treatments. Exclusion criteria included evidence of a urinary tract infection, bladder cancer, or other forms of chronic cystitis. Patients received 400 mg of Pentosan Polysulfate (PP) encapsulated into liposomes as an intravesical instillation performed every 2 weeks for 3 months. Baseline and post treatment outcome measures were obtained that included the O'Leary-Sant Interstitial Cystitis Symptom and Problem Questionnaire and the Pelvic Pain and Urgency/Frequency Patient symptom Scale tests. A total of 37 instillations were used and no adverse events occurred. Clinically significant decreases in symptom scores greater than 50% were seen in virtually all outcome measures at 3 month follow up. All subjects reported remarkable subjective improvement in pain symptoms marked by decreased use of narcotics and increased enjoyment of daily activities. No patients developed systemic symptoms or poor tolerance of the instillations. Intravesical Pentosan Polysulfate encapsulated into liposomes can significantly decrease frequency, urgency, pain and improve quality of life for two months after deployment. Additional studies are needed to determine cellular effects of glycosaminoglycan restoration, ideal doses, dosing intervals, safety and cost-effectiveness of this therapy.
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Quantitative and functional characterization of the hyper-conserved protein of prochlorococcus and marine synechococcus.
PLoS ONE
PUBLISHED: 01-01-2014
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A large fraction of any bacterial genome consists of hypothetical protein-coding open reading frames (ORFs). While most of these ORFs are present only in one or a few sequenced genomes, a few are conserved, often across large phylogenetic distances. Such conservation provides clues to likely uncharacterized cellular functions that need to be elucidated. Marine cyanobacteria from the Prochlorococcus/marine Synechococcus clade are dominant bacteria in oceanic waters and are significant contributors to global primary production. A Hyper Conserved Protein (PSHCP) of unknown function is 100% conserved at the amino acid level in genomes of Prochlorococcus/marine Synechococcus, but lacks homologs outside of this clade. In this study we investigated Prochlorococcus marinus strains MED4 and MIT 9313 and Synechococcus sp. strain WH 8102 for the transcription of the PSHCP gene using RT-Q-PCR, for the presence of the protein product through quantitative immunoblotting, and for the protein's binding partners in a pull down assay. Significant transcription of the gene was detected in all strains. The PSHCP protein content varied between 8±1 fmol and 26±9 fmol per ug total protein, depending on the strain. The 50 S ribosomal protein L2, the Photosystem I protein PsaD and the Ycf48-like protein were found associated with the PSHCP protein in all strains and not appreciably or at all in control experiments. We hypothesize that PSHCP is a protein associated with the ribosome, and is possibly involved in photosystem assembly.
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CART in the regulation of appetite and energy homeostasis.
Front Neurosci
PUBLISHED: 01-01-2014
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The cocaine- and amphetamine-regulated transcript (CART) has been the subject of significant interest for over a decade. Work to decipher the detailed mechanism of CART function has been hampered by the lack of specific pharmacological tools like antagonists and the absence of a specific CART receptor(s). However, extensive research has been devoted to elucidate the role of the CART peptide and it is now evident that CART is a key neurotransmitter and hormone involved in the regulation of diverse biological processes, including food intake, maintenance of body weight, reward and addiction, stress response, psychostimulant effects and endocrine functions (Rogge et al., 2008; Subhedar et al., 2014). In this review, we focus on knowledge gained on CART's role in controlling appetite and energy homeostasis, and also address certain species differences between rodents and humans.
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Improving dental experiences by using virtual reality distraction: a simulation study.
PLoS ONE
PUBLISHED: 01-01-2014
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Dental anxiety creates significant problems for both patients and the dental profession. Some distraction interventions are already used by healthcare professionals to help patients cope with unpleasant procedures. The present study is novel because it a) builds on evidence that natural scenery is beneficial for patients, and b) uses a Virtual Reality (VR) representation of nature to distract participants. Extending previous work that has investigated pain and anxiety during treatment, c) we also consider the longer term effects in terms of more positive memories of the treatment, building on a cognitive theory of memory (Elaborated Intrusions). Participants (n?=?69) took part in a simulated dental experience and were randomly assigned to one of three VR conditions (active vs. passive vs. control). In addition, participants were distinguished into high and low dentally anxious according to a median split resulting in a 3×2 between-subjects design. VR distraction in a simulated dental context affected memories a week later. The VR distraction had effects not only on concurrent experiences, such as perceived control, but longitudinally upon the vividness of memories after the dental experience had ended. Participants with higher dental anxiety (for whom the dental procedures were presumably more aversive) showed a greater reduction in memory vividness than lower dental-anxiety participants. This study thus suggests that VR distractions can be considered as a relevant intervention for cycles of care in which people's previous experiences affect their behaviour for future events.
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Evidence-based diabetes nutrition therapy recommendations are effective: the key is individualization.
Diabetes Metab Syndr Obes
PUBLISHED: 01-01-2014
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Current nutrition therapy recommendations for the prevention and treatment of diabetes are based on a systematic review of evidence and answer important nutrition care questions. First, is diabetes nutrition therapy effective? Clinical trials as well as systematic and Cochrane reviews report a ~1%-2% lowering of hemoglobin A1c values as well as other beneficial outcomes from nutrition therapy interventions, depending on the type and duration of diabetes and level of glycemic control. Clinical trials also provide evidence for the effectiveness of nutrition therapy in the prevention of diabetes. Second, are weight loss interventions important and when are they beneficial? Modest weight loss is important for the prevention of type 2 diabetes and early in the disease process. However, as diabetes progresses, weight loss may or may not result in beneficial glycemic and cardiovascular outcomes. Third, are there ideal percentages of macronutrients and eating patterns that apply to all persons with diabetes? There is no ideal percentage of macronutrients and a variety of eating patterns has been shown to be effective for persons with diabetes. Treatment goals, personal preferences (eg, tradition, culture, religion, health beliefs, economics), and the individual's ability and willingness to make lifestyle changes must all be considered by clinicians and/or educators when counseling and educating individuals with diabetes. A healthy eating pattern emphasizing nutrient-dense foods in appropriate portion sizes, regular physical activity, and support are priorities for all individuals with diabetes. Reduced energy intake for persons with prediabetes or type 2 diabetes as well as matching insulin to planned carbohydrate intake are intervention to be considered. Fourth, is the question of how to implement nutrition therapy interventions in clinical practice. This requires nutrition care strategies.
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Outcomes of Breast Cancer in Brazil Related to Health Care Coverage: A Retrospective Cohort Study.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 10-28-2013
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Breast cancer is the most common malignancy in women in Brazil. Differences between patients with public versus private healthcare coverage about general characteristics, disease presentation, treatment of primary tumors, and clinical outcomes have not been fully investigated.
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Nutrition therapy recommendations for the management of adults with diabetes.
Diabetes Care
PUBLISHED: 10-09-2013
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There is no standard meal plan or eating pattern that works universally for all people with diabetes. In order to be effective, nutrition therapy should be individualized for each patient/client based on his or her individual health goals; personal and cultural preferences; health literacy and numeracy; access to healthful choices; and readiness, willingness, and ability to change. Nutrition interventions should emphasize a variety of minimally processed nutrient dense foods in appropriate portion sizes as part of a healthful eating pattern and provide the individual with diabetes with practical tools for day-to-day food plan and behavior change that can be maintained over the long term.
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Measurement of Novel Biomarkers to Predict Chronic Heart Failure Outcomes and Left Ventricular Remodeling.
J Cardiovasc Transl Res
PUBLISHED: 10-01-2013
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Myocardial remodeling is pivotal in the progression and complication of chronic heart failure (HF). We assessed serial measurement of five biomarkers with biologic links to remodeling (biglycan, secreted frizzled-related protein 3, endostatin, insulin-like growth factor binding protein 7 [IGFBP7], mimecan) in 142 patients with HF followed through 882 office visits. IGFBP7 and mimecan were most associated with events; in fully adjusted models, lower IGFBP7 concentrations across visits independently predicted fewer events (odds ratio [OR]?=?0.83; 95 % confidence interval [CI]?=?0.73-0.95, p?=?0.01). Subjects with rising mimecan had greater decrease in left ventricular end diastolic (p?=?0.07) and systolic (p?=?0.01) volumes, greater increase in ejection fraction (p?=?0.02), and had lowest event rates. Statistical models suggested several HF medications might lead to changes in both IGFBP7 and mimecan values. The results suggest serial measurement of IGFBP7 provides prognostic information, while changes in mimecan provide unique information regarding myocardial remodeling.
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Seasonal changes in the antibody responses against Plasmodium falciparum merozoite surface antigens in areas of differing malaria endemicity in Indonesia.
Malar. J.
PUBLISHED: 09-10-2013
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The transmission of malaria in Indonesia is highly heterogeneous spatially and seasonally. Anti-malaria antibody responses can help characterize this variation. In the present study antibody responses to Plasmodium falciparum MSP-1 and AMA-1 were measured to assess the transmission intensity in a hypo-endemic area of Purworejo and a meso-endemic area of Lampung during low and high transmission seasons.
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Analysis of start-up, retention, and adherence in ALS clinical trials.
Neurology
PUBLISHED: 09-04-2013
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To investigate predictors of trial start-up times, high attrition, and poor protocol adherence in amyotrophic lateral sclerosis (ALS) trials.
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?-Catenin mutation status and outcomes in sporadic desmoid tumors.
Oncologist
PUBLISHED: 08-19-2013
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Mutations in the gene-encoding ?-catenin, CTNNB1, are highly prevalent in sporadic desmoid tumors and may predict the risk for recurrence. We sought to determine the prevalence of CTNNB1 mutations in a large cohort of sporadic desmoid tumors and to determine whether CTNNB1 mutation status correlates with disease outcome.
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Cosegregation of Focal Segmental Glomerulosclerosis in a Family with Familial Partial Lipodystrophy due to a Mutation in LMNA.
Nephron Clin Pract
PUBLISHED: 07-24-2013
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Background and Aim: Focal segmental glomerulosclerosis (FSGS) is a common cause of idiopathic nephrotic syndrome in adults (35%). A number of genetic and familial forms of FSGS have been recognized. Here, we report a large pedigree with a pathogenic mutation in LMNA (R349W) in which four members were found to have biopsy-proven FSGS. The LMNA gene codes for lamins A and C, major components of the nuclear lamina which function in nuclear architecture, integrity and the regulation of gene expression. Methods: Pedigree screening and mutation analysis of LMNA gene in all family members. Renal biopsies were performed in proteinuric patients. A molecular 3D model of the familial LMNA mutation was constructed. Results: There were a total of 16 affected members from four generations, 12 of whom were found to carry the germline LMNA mutation. All affected adults had clinical features of familial partial lipodystrophy (FPLD) of the non-Dunnigan variety. Four patients within the same generation presented with a variable degree of renal impairment and proteinuria. Renal biopsies from all four revealed FSGS. The familial mutation is a missense change (R349W) in exon 6 of LMNA (c.1045C>T). Conclusions: We report a genetic link between LMNA and biopsy-proven FSGS in a large pedigree with FPLD. This unexpected association extends the disease spectrum of LMNA to the kidney and suggests that the physiological role of LMNA could be relevant to the maintenance of glomerular structure and function. © 2013 S. Karger AG, Basel.
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Alcohol consumption in young adults: The role of multisensory imagery.
Addict Behav
PUBLISHED: 07-19-2013
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Little is known about the subjective experience of alcohol desire and craving in young people. Descriptions of alcohol urges continue to be extensively used in the everyday lexicon of young, non-dependent drinkers. Elaborated Intrusion (EI) Theory contends that imagery is central to craving and desires, and predicts that alcohol-related imagery will be associated with greater frequency and amount of drinking. This study involved 1535 age stratified 18-25year olds who completed an alcohol-related survey that included the Imagery scale of the Alcohol Craving Experience (ACE) questionnaire. Imagery items predicted 12-16% of the variance in concurrent alcohol consumption. Higher total Imagery subscale scores were linearly associated with greater drinking frequency and lower self-efficacy for moderate drinking. Interference with alcohol imagery may have promise as a preventive or early intervention target in young people.
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Multiple Service Use: The impact of consistency in service quality for vulnerable youth.
Child Abuse Negl
PUBLISHED: 07-17-2013
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Little is known about the way in which variations in service quality influence outcomes when youth are clients of more than one service system. This article reports on a study of 1,210 adolescents (aged 13-17 years), half were concurrent clients of two or more services and half were not involved in two or more services. Youth completed a self-report questionnaire administered by a trained interviewer. It was hypothesized that youth reporting two positive service experiences would report lower risks, higher resilience, and better outcomes than youth reporting inconsistent or two negative service experiences and that their resilience, risks, and outcomes would be similar to those of youth not involved in two or more services. MANCOVA was used to determine the relationship among service quality and resilience, risk, and outcomes with four covariates that assessed family and neighborhood environments, history of abuse and neglect, and chronic need. Results indicate that service quality had an effect on resilience, risks, and outcomes. These relationships were mediated quite strongly by the influence of the risks youth faced in their neighborhoods and to a lesser extent by the other three covariates. Of the three dependent variables, risk appeared to be the most consistently influenced by all the covariates, and it also differentiated service experience groups. Results point to the importance of services developing strategies to effectively address risks confronted by youth and also to ensure that when more than one service is involved with youth, consistency in service delivery is achieved.
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Intracellular antibody receptor TRIM21 prevents fatal viral infection.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 07-09-2013
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Host species have evolved mechanisms that can inhibit pathogen replication even after a cell has been successfully invaded. Here we show that tripartite-motif protein 21 (TRIM21), a ubiquitously expressed E3 ubiquitin ligase that targets viruses inside the cytosol, protects mice against fatal viral infection. Upon infection with mouse adenovirus-1, naive mice lacking TRIM21 succumb to encephalomyelitis within 7 d. In contrast, wild-type mice rapidly up-regulate TRIM21 and control viremia. Trim21 heterozygous mice have a haploinsufficiency phenotype in which reduced TRIM21 expression leads to a viral load that is higher than wild types but lower than knockouts. TRIM21 is a high-affinity antibody receptor that allows antibodies to operate inside an infected cell. In passive transfer experiments at high viral dose, antisera that fully protects wild-type mice fails to protect most Trim21 knockout animals. These results demonstrate that TRIM21 provides potent antiviral protection and forms an important part of the humoral immune response.
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Brief guided imagery and body scanning interventions reduce food cravings.
Appetite
PUBLISHED: 07-06-2013
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Elaborated Intrusion (EI) Theory proposes that cravings occur when involuntary thoughts about food are elaborated; a key part of elaboration is affectively-charged imagery. Craving can be weakened by working memory tasks that block imagery. EI Theory predicts that cravings should also be reduced by preventing involuntary thoughts being elaborated in the first place. Research has found that imagery techniques such as body scanning and guided imagery can reduce the occurrence of food thoughts. This study tested the prediction that these techniques also reduce craving. We asked participants to abstain from food overnight, and then to carry out 10min of body scanning, guided imagery, or a control mind wandering task. They rated their craving at 10 points during the task on a single item measure, and before and after the task using the Craving Experience Questionnaire. While craving rose during the task for the mind wandering group, neither the guided imagery nor body scanning group showed an increase. These effects were not detected by the CEQ, suggesting that they are only present during the competing task. As they require no devices or materials and are unobtrusive, brief guided imagery strategies might form useful components of weight loss programmes that attempt to address cravings.
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Prediction of late disease recurrence and extended adjuvant letrozole benefit by the HOXB13/IL17BR biomarker.
J. Natl. Cancer Inst.
PUBLISHED: 06-28-2013
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Biomarkers to optimize extended adjuvant endocrine therapy for women with estrogen receptor (ER)-positive breast cancer are limited. The HOXB13/IL17BR (H/I) biomarker predicts recurrence risk in ER-positive, lymph node-negative breast cancer patients. H/I was evaluated in MA.17 trial for prognostic performance for late recurrence and treatment benefit from extended adjuvant letrozole.
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Motivational interviewing to reduce cardiovascular risk in African American and Latina women.
West J Nurs Res
PUBLISHED: 06-26-2013
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Cardiovascular disease (CVD) is the leading cause of death for women, and disproportionally so for African American and Latina women. CVD is largely preventable and many risks can be attributable to health behaviors, implementing and sustaining positive health behaviors is a challenge. Motivational interviewing is one promising intervention for initiating behavior change. The purpose of this review was to identify, synthesize, and critically analyze the existing literature on the use of motivational interviewing as a behavioral intervention to reduce CVD risk among African American and Latina women. Seven studies were identified that met inclusion criteria. Results of this review suggest that motivational interviewing has mixed results when used to reduce cardiovascular risk factors in African American and Latina women. More research using a standardized motivational interviewing approach is needed to definitively determine if it is an effective behavioral intervention to reduce CVD risk when used in populations of African American and Latina women.
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Human skin keratinocytes can be reprogrammed to express neuronal genes and proteins after a single treatment with decitabine.
Biores Open Access
PUBLISHED: 06-07-2013
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Patient-specific cell replacement therapy is fast becoming the future of medicine, requiring safe, effective methods for reprogramming a patients own cells. Previously, we showed that a single transient transfection with a plasmid encoding Oct4 was sufficient to reprogram human skin keratinocytes (HSKs), and that this transfection resulted in a decrease in global DNA methylation. In more recent work we showed that decreasing global DNA methylation using the U.S. Food and Drug Administration-approved cancer treatment drug decitabine was sufficient to induce expression of endogenous Oct4. Here we report that a single treatment with decitabine, followed by 5 days in a defined neuronal transformation medium, then 7 days in a neuronal maintenance medium is sufficient to convert HSKs into cells that change their morphology substantially, gain expression of neuronal markers, and lose expression of keratinocyte markers. Within 1 week of treatment the cells express mRNA for ?3-tubulin and doublecortin, and at the end of 2 weeks express mRNA for NeuN, FOXP2, and NCAM1. Additionally, at the end of this protocol, neurofilament-1, nestin, synapsin, FOXP2, and GluR1 proteins are detectable by immunostaining. Thus, we demonstrate a simple method that begins the process for producing cells for cell replacement therapies without using exogenously introduced DNA.
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Development and validation of the cough severity index: a severity index for chronic cough related to the upper airway.
Laryngoscope
PUBLISHED: 06-04-2013
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To develop and validate a cough severity index (CSI) which quantifies patients symptoms associated with upper airway chronic cough and to provide a tool for treatment outcome measures.
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Metronomic therapy is an effective salvage treatment for heavily pre-treated relapsed/refractory multiple myeloma.
Haematologica
PUBLISHED: 05-28-2013
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Relapsed/refractory multiple myeloma represents a major challenge in multiple myeloma therapy. For patients with relapsed/refractory multiple myeloma, we developed a treatment schema of metronomically scheduled drug therapy. We identified 186 patients who had been treated with metronomic therapy between March 2004 and January 2012 with a median follow up of 24.2 months. Median age was 61 years (range 36-83). Median number of prior therapies was 14 (range 1-51). Median number of completed metronomic therapy cycles was 1 (range 1-5), while 45 of 186 (25%) received 2 or more cycles. Responses included complete remission in 11 of 186 patients (6%), very good partial remission in 12 of 186 (7%), partial remission in 65 of 179 (36%), and minimal response in 29 of 186 (16%), for an overall response rate of 63% (117 of 186). Median overall survival and progression-free survival were 11.2 and 3.6 months, respectively. Hematologic toxicity grading was problematic as 146 of 186 (78%) of patients presented with at least grade 2 thrombocytopenia within 90 days prior to starting metronomic therapy. Grade 4 leukopenia, anemia, and/or thrombocytopenia following metronomic therapy occurred in 108 of 186 (58%), 12 of 186 (6%), and 147 of 186 (79%) patients, respectively. Incidence of grade 3-4 neutropenic fever was 4 of 186 (2%). Most patients (177 of 186, 95%) were treated in an outpatient unit and secondary admissions due to regimen-related toxicity occurred in 37 of 186 (20%). Treatment-related mortality was evident in 2 of 186 (1%). In conclusion, metronomic therapy is an effective late salvage treatment in relapsed/refractory multiple myeloma, with a high overall response rate and a favorable toxicity profile.
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Assessing vividness of mental imagery: The Plymouth Sensory Imagery Questionnaire.
Br J Psychol
PUBLISHED: 05-21-2013
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Mental imagery may occur in any sensory modality, although visual imagery has been most studied. A sensitive measure of the vividness of imagery across a range of modalities is needed: the shorter version of Betts Questionnaire upon Mental Imagery (Sheehan, , J. Clin. Psychology, 23, 386) uses outdated items and has an unreliable factor structure. We report the development and initial validation of the Plymouth Sensory Imagery Questionnaire (Psi-Q) comprising items for each of the following modalities: Vision, Sound, Smell, Taste, Touch, Bodily Sensation, and Emotional Feeling. An exploratory factor analysis on a 35-item form indicated that these modalities formed separate factors, rather than a single imagery factor, and this was replicated by confirmatory factor analysis. The Psi-Q was validated against the Spontaneous Use of Imagery Scale (Reisberg et al., , Appl. Cogn. Psychology, 17, 147) and Marks (, J. Mental Imagery, 19, 153) Vividness of Visual Imagery Questionnaire-2 (VVIQ-2). A short 21-item form comprising the best three items from the seven factors correlated with the total score and subscales of the full form, and with the VVIQ-2. Inspection of the data shows that while visual and sound imagery is most often rated as vivid, individuals who rate one modality as strong and the other as weak are not uncommon. Findings are interpreted within a working memory framework and point to the need for further research to identify the specific cognitive processes underlying the vividness of imagery across sensory modalities.
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PYY3-36 and pancreatic polypeptide reduce food intake in an additive manner via distinct hypothalamic dependent pathways in mice.
Obesity (Silver Spring)
PUBLISHED: 05-14-2013
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Peptide YY (PYY3-36) and pancreatic polypeptide (PP) potently inhibit food intake in rodents and humans, however, it is unclear whether they have any synergistic/additive interaction in decreasing food intake.
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Assessing malaria transmission in a low endemicity area of north-western Peru.
Malar. J.
PUBLISHED: 05-10-2013
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Where malaria endemicity is low, control programmes need increasingly sensitive tools for monitoring malaria transmission intensity (MTI) and to better define health priorities. A cross-sectional survey was conducted in a low endemicity area of the Peruvian north-western coast to assess the MTI using both molecular and serological tools.
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Serial measurement of galectin-3 in patients with chronic heart failure: results from the ProBNP Outpatient Tailored Chronic Heart Failure Therapy (PROTECT) study.
Eur. J. Heart Fail.
PUBLISHED: 05-10-2013
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Galectin-3 is a prognostic heart failure (HF) biomarker that may mediate cardiac fibrosis. We examined the value of serial galectin-3 measurement for prognosis and response to therapy in chronic HF.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.